The objective of this proposed research is to determine whether characteristic mutation spectra (types and frequencies) can be induced at or proximal to the HPRT locus in normal human fibroblasts exposed to various forms of ionizing radiation. If unique mutational spectra can be demonstrated, then this can serve as a molecular signature to differentiate low and high LET radiation induced genetic damage from that which occur spontaneously. The specific aims are: 1) to determine whether the spectra of point mutations induced by gamma-rays and alpha-particles are significantly different from that which occur spontaneously; and 2) to determine whether the size distribution of deletions induced by various forms of radiation is dependent on the quality of radiation and can be differentiated from that which occurs spontaneously.